Method for vascular occulusive therapy in gastrointestinal system

ABSTRACT

A method for treating a blood vessel in a wall forming a gastrointestinal tract of a body of a mammal. At least one nonaqueous solution is introduced from the gastrointestinal tract into the vessel. A nonbiodegradable solid is formed in the vessel in the vicinity of a portion of the vessel from the least one nonaqueous solution to create an occlusion in the vessel and thus terminate blood flow to the vessel distal of the occlusion.

This application is a continuation-in-part of U.S. patent applicationSer. No. 09/232,056 filed Jan. 15, 1999 and claims priority to U.S.provisional patent application Ser. No. 60/111,884 filed Dec. 11, 1998,the entire contents of each of which are incorporated herein by thisreference.

This invention pertains to the treatment of blood vessels and, moreparticularly, to the treatment of dilated veins.

Blood vessels, and specifically veins, in the gastrointestinal tract ofa body can often become enlarged. For example, a vein which becomesenlarged and lengthened is known as a varix. Such varices can occur inthe wall of the gastrointestinal tract, for example in the vicinity ofthe lower esophageal sphincter. A dilated vein at the margin of the anusor nearby within the rectum is known as a hemorrhoid. An erosion in themucous membrane of the gastrointestinal tract is known as an ulcer.Bleeding from ulcers can be either from veins or arteries. Varices,hemorrhoids and ulcers are more suspectable to undesirable bleeding thannormal vessels.

Sclerotherapy is used to treat bleeding of esophageal varices. However,rebleeding is still common in patients receiving sclerotherapy. Inaddition, the injection of sclerosing agents induces various local andsystemic complications. Ligation was developed in an attempt to providean endoscopic therapy that would be at least as effective assclerotherapy but have fewer complications. Unfortunately, relativelylarge vessels can be difficult to ligate. In addition, the ligationprocedure can cause tears in the vessel. Hemorrhoids have been treatedin the same manner as varices, but these treatment techniques sufferfrom the same disadvantages discussed above.

For patients with severely bleeding ulcers, surgery may be required tocauterize the vasculature in the vicinity of the ulcer. Unfortunately,surgical intervention is a major operation with all attendantmorbidities, mortality and risk of failure requiring further surgery.

As can be seen from the foregoing, there is a need for a new andimproved method for treating varices, hemorrhoids and gastric ulcers.

In general, it is an object of the present invention to provide aminimally invasive method for injecting a material into a vessel in thegastrointestinal system of the body to substantially occlude the vessel.

Another object of the invention is to provide a method of the abovecharacter in which the injected material is a nonbiodegradable material.

Another object of the invention is to provide a method of the abovecharacter in which the material is injected as at least one solution andthereafter forms a solid.

Another object of the invention is to provide a method of the abovecharacter in which the at least one solution includes a solution fromwhich a nonbiodegradable solid precipitates.

Another object of the invention is to provide a method of the abovecharacter in which the solution includes a biocompatible polymer and abiocompatible solvent.

Additional objects and features of the invention will appear from thefollowing description from which the preferred embodiments are set forthin detail in conjunction with the accompanying drawings.

FIG. 1 is a perspective view of an apparatus for use in the method fortreating vessels of the present invention.

FIG. 2 is a cross-sectional view of a portion of the apparatus of FIG. 1taken along the line 2—2 of FIG. 1.

FIG. 3 is an enlarged side view of the distal portion of the apparatusof FIG. 1 taken along the line 3—3 of FIG. 1.

FIG. 4 is an enlarged side view, similar to FIG. 3, of the distalportion of another embodiment of the apparatus for use in the method fortreating vessels of the present invention.

FIG. 5 is a cross-sectional view of a proximal portion of the apparatusof FIG. 1 taken along the line 5—5 of FIG. 1.

FIG. 6 is a schematic view of the apparatus of FIG. 1 practicing themethod of the present invention for treating varices in the vicinity ofthe esophageal sphincter.

FIG. 7 is an enlarged view of a portion of the esophagus and cardia ofFIG. 6, taken along the line 7—7 of FIG. 6, showing the method step ofFIG. 6.

FIG. 8 is a cross-sectional view of a treated varix in the area of theesophagus and cardia taken along the line 8—8 of FIG. 7.

FIG. 9 is an enlarged view, similar to FIG. 7, of a portion of theesophagus and cardia showing the apparatus of FIG. 1 practicing themethod of the present invention for treating ulcers in the cardia.

FIG. 10 is a cross-sectional view of a treated ulcer in the cardia takenalong the line 10—10 of FIG. 9.

FIG. 11 is a schematic view of a step of method of the present inventionfor treating hemorrhoids in the anal canal.

FIG. 12 is a cross-sectional view of a treated hemorrhoid in the analcanal taken along the line 12—12 of FIG. 11.

In general, a method for treating a blood vessel in a wall forming agastrointestinal tract of a body of a mammal is provided. At least onenonaqueous solution is introduced from the gastrointestinal tract intothe vessel. A nonbiodegradable solid is formed in the vessel in thevicinity of a portion of the vessel from the least one nonaqueoussolution to create an occlusion in the vessel and thus terminate bloodflow to the vessel distal of the occlusion.

The method of the present invention can be performed with an apparatusof the type shown in FIG. 1. Apparatus or medical device 21 showntherein includes a probe member or probe 22 having an optical viewingdevice 23. A needle assembly 26 is slidably carried by probe 22.Treatment device 21 further includes a supply assembly 27 mounted to theproximal end portion of needle assembly 26.

A conventional or other suitable gastroscope or endoscope can be usedfor probe 22. The exemplary probe 22 shown in FIG. 1 is an Olympus CFType 40L/I endoscope made by Olympus Corporation of Tokyo Japan. Probe22 includes a flexible elongate tubular member or insertion tube 31having proximal and distal extremities 31 a and 31 b and a distal face32. Insertion tube 31 has been sectioned in FIG. 1 so that only aportion of proximal extremity 31 a and distal extremity 31 b is shown. Ahandle means or assembly is coupled to proximal extremity 31 a of theinsertion tube 31 and includes a conventional handle 33. The tubularinsertion tube 31 is provided with a plurality of bores or passagewaysextending from proximal extremity 31 a to distal extremity 31 b. Aplurality of five such passageways, including a central passageway 36,are shown in FIG. 2.

An optical viewing device 23 is formed integral with conventional probe22 and has an optical element or objective lens 37 carried by thecentral passageway 36 of insertion tube 31. The lens 37 has a field ofview at distal face 32 which permits the operator to view forwardly ofinsertion tube distal extremity 31 b. Optical viewing device 37 furtherincludes an eye piece 41 mounted on the proximal end of handle 33.Second and third illumination passageways 42 are provided in insertiontube 31 peripherally of central passageway 36 for carrying respectivelight fiber assemblies or light guides 43. A connection cable 46, aportion of which is shown in FIG. 1, extends from handle 33 to aconventional light source 47. First and send light guides 43 extendthrough insertion tube 31 and cable 46 for providing illuminationforwardly of insertion tube 31.

A working passageway or channel 51 is further provided in insertion tube31 and extends to a side port 52 formed in handle 33. An additionalpassageway 56 extends through insertion tube 31 and can be used as anair and/or water outlet. Insertion tube 31 is flexible so as tofacilitate its insertion and advancement through a body and is providedwith a bendable distal end for selectively directing distal face 32 in adesired direction. A plurality of finger operable controls 57 areprovided on handle 33 for, among other things, operating the bendabledistal end of insertion tube 31 and the supply and removal of fluidsthrough the insertion tube 31.

Needle assembly 26 can be of any conventional type such as a modifiedsclerotherapy needle similar to the Bard® Flexitip™ needle manufacturedby C. R. Bard, Inc. of Billerica, Md. Needle assembly 26 includes aneedle member or needle 61 having a proximal end portion 61 a and adistal end portion 61 b and an optional sleeve member or sleeve 62having a proximal end portion 62 a and a distal end portion 62 b. Sleeve62 is made from any suitable material such as plastic and has a lumenextending longitudinally therethrough for receiving the needle 61. Thesleeve 62 and the needle 61 are slidable relative to each other in alongitudinal direction. Needle 61 and sleeve 62 can be slidably disposedwithin working channel 51 and side port 62 of insertion tube 31 and eachhave a length so that when distal end portions 61 b and 62 b areextending from distal extremity 31 b of the insertion tube 31 orotherwise in the vicinity of distal face 32, proximal end portions 61 aand 62 a are accessible at side port 52.

The hollow needle 61 has a passage 63 extending longitudinallytherethrough from proximal end portion 61 a to distal end portion 61 b.The modified needle distal end portion 61 b is made from any suitablematerial such as stainless steel and has a size ranging from 16 to 28gauge and preferably ranging from 23 to 26 gauge. As shown most clearlyin FIG. 3, the distal end portion 61 b has a cylindrical wall 66 forforming internal passage 63 and also has a sharpened or beveled distalend 67 formed in part by a tapered end surface 68. At least one opening71 is provided in distal end portion 61 and can include or consist of anopening 71 a provided in tapered end surface 68. As an alternative to orin addition to opening 71 a, at least one and as shown a plurality ofopenings 71 can be provided in cylindrical wall 66. A plurality of twoopenings 71 b and two additional openings 71 c are provided in wall 66.Openings 71 b are diametrically disposed relative to each other, so asto be 180° apart, and openings 71 c are also diametrically disposedrelative to each other but offset 90° from openings 71 b. The openings71 c are spaced longitudinally behind the openings 71 b. Openings 71 band 71 c can be any suitable shape or size and are shown as beingelongate or oblong in shape. It should be appreciated that a needledistal end portion 61 b having only openings 71 b or openings 71 c canbe provided and be within the scope of the present invention. In oneembodiment of needle 61, tapered surface 68 is closed and openings 71provided only in cylindrical wall 66.

Another embodiment of the modified distal end portion of the needle 61is shown in FIG. 4. Distal end portion 61 b′ therein has a sharpened orpointed distal end 76 which is generally conical in shape. No opening 71is provided in the closed pointed end 76. A plurality of threecircumferentially-disposed openings 71 d are provided in cylindricalwall 66 proximal of pointed end 76. Openings 71 d are circumferentiallyspaced apart at separation angles of approximately 120°. A second set ofthree openings 71 e extend through cylindrical wall 66 proximal ofopenings 71 d. Openings 71 e are also circumferentially spaced apart atseparation angles of approximately 120°. The openings 71 e are angularlyoffset about the centerline of distal end portion 61 b′ relative to theopening 71 d.

A fluid connector 81 is secured to proximal end portion 61 a of needle61 and a gripping member or grip 82 is secured to the proximal endportion 62 a of the sleeve 62 (see FIG. 1). Fluid connector 81 includesfirst and second luer fitting portions 83 and 84, or any other suitablefitting portions, which communicate with passage 63 in needle 61. Firstluer fitting portion 83 is capped in FIG. 1. Fluid connector 81 and grip82 are longitudinally movable relative to each other so as to causerelative longitudinal movement between needle 61 and sleeve 62. Morespecifically, grip 82 can be slid forwardly and rearwardly on proximalend portion 61 a of the needle 61 relative to fluid connector 81.Movement of grip 82 forwardly relative to fluid connector 81 causesdistal end portion 62 b of sleeve 62 to extend fully over distal endportion 61 b of the needle 61 so that the needle has fully retractedwithin sleeve 62. Conversely, movement of grip 82 rearwardly relative tofluid connector 81 causes sleeve distal end portion 62 b to retractrelative to needle distal end portion 61 b so as to expose the needledistal end portion 61 b.

The handle means of treatment device 21 includes supply assembly 27coupled to proximal extremity 31 a of insertion tube 31 (see FIG. 1).More specifically, supply assembly 27 is secured to the proximalextremity of needle assembly 26. The supply assembly 27 is includedwithin the means of treatment device 21 for introducing a liquid orsolution through passage 63 of needle 61 and out one or more of theopenings 71 provided in the needle distal end portion 61 b. Supplyassembly 27 comprises a conventional syringe or first syringe 91 havinga reservoir or barrel 92 provided with any suitable fitting portion suchas luer fitting portion 93 at the forward end thereof and a plunger 94for dispelling liquid within barrel 92 through luer fitting portion 93.The supply assembly 27 optionally includes second and third reservoirsin the form of second and third syringes 96 and 97. The second syringe96 is filled with dimethyl sulfoxide (DMSO) or any other suitableliquid. The third syringe 97 is filled with a saline solution or anyother suitable aqueous or physiologic solution.

A manifold assembly or manifold 98 is provided for coupling syringes 91,96 and 97 to fluid connector 81. In one embodiment, the manifold 98 hasa plurality of three stop cocks 101-103 and a plurality of at least twoand as shown a plurality of four ports or luer fitting portions. A firstluer fitting portion 104 cooperatively mates with the forward luerfitting portion 93 of syringe 91. A second luer fitting portion 106cooperatively mates with second luer fitting portion 84 of the fluidconnector 81. Third and fourth luer fitting portions 107 and 108 areadditionally provided. The third luer fitting portion 107 is connectedby a tube 109, a portion of which is shown in FIG. 1, to second syringe96 and the fourth luer fitting portion 108 is connected by a tube 110, aportion of which is shown in FIG. 1, to third syringe 97. The stop cocks101-103 operate in a conventional manner to direct fluid flow betweenthe luer fitting portions 104 and 106-108. In a further embodiment ofthe invention (not shown), syringe 91 can be secured directly to fluidconnector 81 or the proximal end portion 61 a of needle 61. It should beappreciated that manifold 98 can alternatively be provided with lessthan or greater than four luer fitting portions or be of any otherconfiguration for coordinating fluid flow from a plurality of syringesor other fluid reservoirs.

Supply assembly 27 further includes an optional delivery device or gun111 for supplying a plurality of discrete preselected amounts of thefluid within barrel 92 to needle 61 (see FIGS. 1 and 5). Gun 111 has acylindrical housing 112 made from plastic or any other suitable materialfor receiving syringe barrel 92. Housing 112 is formed from a baseportion 113 and a cover portion 114 pivotally secured to the baseportion 113 by hinge 116. A latch 117 is pivotally coupled to the coverportion 114 for engaging base portion 113 and thereby locking the coverportion 114 in a closed position. Housing 112 has a forward opening 118for receiving luer fitting portion 93 of the syringe 91. A handle 126made from plastic or any other suitable material depends from baseportion 113. The handle 126 has an internal cavity 127. First and secondspaced-apart reinforcing members 128 and 129 extend downwardly from thebase portion 113 at the front and rear of handle 126. The reinforcingmembers 128 and 129 are longitudinally aligned and each provided with abore 132 extending longitudinally therethrough and opening into internalcavity 127. A rod 136 made from plastic or any other suitable materialis slidably disposed within bores 132. The rod 136 has a paddle 137extending upwardly from the rear thereof perpendicularly to thelongitudinal axis of the rod. Paddle 137 is adapted to engage the end ofsyringe plunger 94. A ring 138 sized for receiving a finger of a humanhand extends rearwardly from paddle 137 for facilitating the pulling ofrod 136 rearwardly in bores 132.

Rod 136 and paddle 137 are included within the finger operable means ofgun 111 for causing incremental relative movement between barrel 92 andplunger 94 of the syringe 91. A trigger 141 extends from an opening 142at the front of handle 126 below rod 136. The trigger is slidablydisposed in a direction parallel to the longitudinal axis of rod 136between first and second spaced-apart guides 143 provided in internalcavity 127. Trigger 141 moves between a first or fully extended positionto a second or fully retracted position. A lever 146 is pivotallycoupled to handle 126 by means of a pin 147. The lever 146 has a firstend portion 146 a which extends behind trigger 141 and a second endportion 146 b having a wedge-like shape for engaging one of a pluralityof longitudinally spaced-apart notches formed in the bottom of rod 136.When trigger 141 is pulled rearwardly by the finger of a human hand, thetrigger engages lever first end portion 146 a to cause the lever 146 topivot about pin 147 from a first or home position to a second oroperational position. Lever second end portion 146 b moves forwardlyduring this half-stroke to engage one of notches 148 and cause the rod136 to move forwardly relative to housing 112. The paddle 137 followsrod 136 and incrementally pushes plunger 94 into barrel 92 for each pullof trigger 141.

A fixed stop 151 is provided in handle 126 for limiting the rearwardmovement of trigger 141 and thus determining the incremental amount offluid within barrel 92 dispelled from the syringe 91 with each pull oftrigger 141. The rearward travel of trigger 141 can be selectivelylimited by means of one or more additional pins or stops 152, one ofwhich is shown in FIG. 5. Adjustable limit pin 152 is slidably mountedwithin handle 126 for movement from a first position out of the path oftrigger 141 to a second position within the path of the trigger 141 soas to selectively limit the rearward stroke of trigger 141 when engagedand placed in its second position.

A coil spring 156 or any other suitable biasing number having one endcoupled to a pin 157 mounted within handle 126 and a second end securedto the second end portion 146 b of lever 146 is provided. Spring 156urges lever 146 back to its home position, out of engagement withnotches 148, when the finger pressure on trigger 141 is released. Spring156 causes lever first end portion 146 a to push trigger 141 outwardlyfrom opening 142 to its home position.

A finger operable adjustment mechanism 166 is connected to needleproximal end portion 61 a and sleeve proximal end portion 62 a forcausing longitudinal relative movement between the needle 61 and thesleeve 62. The adjustment mechanism 166 can be of any suitable type foruse with any suitable needle assembly having a needle and sleeve whichare adjustable relative to each other. One embodiment of such anadjustment mechanism 166 is carried by gun 111. As shown in FIG. 1, suchadjustment mechanism 166 has a first or forward post 167 and a second orrear post 168 extending upwardly from the top of cover portion 114. Thelongitudinally spaced-apart posts 167 and 168 extend perpendicularly tobarrels 92. A slidable member or slide bar 171 is slidably mounted in abore (not shown) provided in forward post 167 for forward and rearwardmovement in a direction parallel to barrel 92. A thumb screw 172 havingan enlarged head 172 a is slidably disposed in a bore (not shown)provided in rear post 168. Screw head 172 a abuts rear post 168 and theother end of screw 172 is threadably received within the back end ofslide bar 171. Counterclockwise rotation of thumb screw 172 relative torear post 168 causes slide bar 171 to move rearwardly toward forwardpost 167, while clockwise rotation of the thumb screw 172 results in theslide bar 171 moving forwardly away from post 167. An L-shaped coupler173 is pivotally coupled to the forward end of slide bar 171 by means ofa pin 174. The coupler 173 has first and second spaced-apart arms 176forming a slot 178 therebetween for receiving the central portion ofgrip 82. A screw 179 extends between the arms 176 for locking the armsto grip 82 and thus longitudinally locking sleeve 62 relative to needle61.

Treatment device 21 can be used in the body of a mammal for any suitableprocedure such as the treatment of a vessel, preferably a blood vessel,in the upper portion of the gastrointestinal tract. In one suchprocedure, device 21 is utilized for the treatment of an esophagealvarices. A portion of a human body 184 is shown in FIGS. 6-8 and has aninternal cavity in the form of esophagus 186 extending through a loweresophageal sphincter 187 to a stomach 188. Such cavity is accessible bya natural body opening in the form of mouth 192 and is defined by a wall193. Esophagus 186 is part of the gastrointestinal tract of body 184that extends from mouth 192 to an anus (see FIG. 11).

The esophageal mucosa 196 serves as the inner layer of the intraluminalwall 193 in the esophagus 186 and the gastric mucosa 197 serves as theinner layer of the intramural wall 193 in the stomach 188. Theesophageal mucosa and the gastric mucosa meet at the squamous columnarjunction 198. Wall 193 further includes a muscle layer comprising layerof circular muscle 201 extending beneath mucosa layers 196 and 197 andlayer of longitudinal muscle 202 beneath circular muscle 201. The musclelayers 201 and 202 each extend around the esophagus 186 and the stomach188. Wall 193 further includes a submucosal space 203, that is any spacelocated between mucosa layer 196 or 197 and circular muscle layer 201created by the separation of layer 196 or 197 from muscle layer 201. Thewall 193 has a depth or thickness which includes at least mucosa layers196 or 197, muscle layers 201 and 202 and the submucosal space 203. Thephreno-esophageal ligament 204 and diaphragm 206 extend around theesophagus 186 above the lower esophageal sphincter 187.

A plurality of vessels 207 such as veins, arteries or lymphatic vesselsextend through wall 193. At least some of the vessels have an abnormallydilated and enlarged portion in the form of a varix 208 that protrudesfrom wall 193 (see FIGS. 7 and 8). Each of the varices 208 has proximaland distal portions 208 a and 208 b and, as shown, are in the vicinityof the lower esophageal sphincter 187. The term in the vicinity of thelower esophageal sphincter is defined herein to include at least thelower third of the esophagus, the squamous columnar junction 198, andthe gastric cardia or upper portion of the stomach 188.

In a method of the present invention, at least one nonaqueous solutionis introduced into the vessel or blood vessel 207 to form an occlusionin the blood vessel and thus terminate blood flow to the vessel distalof the occlusion. Although any suitable material can be used with themethod of the present invention, an inert, nonresorbable material ispreferred. One such material comprises at least one solution which whenintroduced into the body forms a nonbiodegradable solid. As used herein,a solid means any substance that does not flow perceptibly undermoderate stress, has a definite capacity for resisting forces which tendto deform it (such as compression, tension and strain) and underordinary conditions retains a definite size and shape; such a solidincludes, without limitation, spongy and/or porous substances. One suchembodiment of the at least one solution is first and second solutionswhich when combined in the body form the nonbiodegradable solid. Anothersuch embodiment is a nonaqueous solution which can be introduced intothe body as a liquid and from which a solid thereafter precipitates. Apreferred embodiment of such a nonaqueous solution is a solution of abiocompatible polymer and a biompatible solvent which can optionallyinclude a contrast agent for facilitating visualization of the solutionin the body.

A particularly preferred augmenting or bulking solution is a compositioncomprising from about 2.5 to about 8.0 weight percent of a biocompatiblepolymer, from about 52 to about 87.5 weight percent of a biocompatiblesolvent and optionally from about 10 to about 40 weight percent of abiocompatible contrast agent having a preferred average particle size ofabout 10 μm or less. It should be appreciated that any percents statedherein which include a contrast agent would be proportionally adjustedwhen the contrast agent is not utilized. Any contrast agent ispreferably a water insoluble biocompatible contrast agent. The weightpercent of the polymer, contrast agent and biocompatible solvent isbased on the total weight of the complete composition. In a preferredembodiment, the water insoluble, biocompatible contrast agent isselected from the group consisting of barium sulfate, tantalum powderand tantalum oxide. In still a further preferred embodiment, thebiocompatible solvent is dimethylsulfoxide (DMSO), ethanol, ethyllactate or acetone.

The term “biocompatible polymer” refers to polymers which, in theamounts employed, are non-toxic, chemically inert, and substantiallynon-immunogenic when used internally in the patient and which aresubstantially insoluble in physiologic liquids. Suitable biocompatiblepolymers include, by way of example, cellulose acetates (includingcellulose diacetate), ethylene vinyl alcohol copolymers, hydrogels(e.g., acrylics), poly(C₁-C₆) acrylates, acrylate copolymers, polyalkylalkacrylates wherein the alkyl and alk groups independently contain oneto six carbon atoms, polyacrylonitrile, polyvinylacetate, celluloseacetate butyrate, nitrocellulose, copolymers of urethane/carbonate,copolymers of styrene/maleic acid, and mixtures thereof. Copolymers ofurethane/carbonate include polycarbonates that are diol terminated whichare then reacted with a diisocyanate such as methylene bisphenyldiisocyanate to provide for the urethane/carbonate copolymers. Likewise,copolymers of styrene/maleic acid refer to copolymers having a ratio ofstyrene to maleic acid of from about 7:3 to about 3:7. Preferably, thebiocompatible polymer is also non-inflammatory when employed in situ.The particular biocompatible polymer employed is not critical and isselected relative to the viscosity of the resulting polymer solution,the solubility of the biocompatible polymer in the biocompatiblesolvent, and the like. Such factors are well within the skill of theart.

The polymers of polyacrylonitrile, polyvinylacetate, poly(C₁-C₆)acrylates, acrylate copolymers, polyalkyl alkacrylates wherein the alkyland alk groups independently contain one to six carbon atoms, celluloseacetate butyrate, nitrocellulose, copolymers of urethane/carbonate,copolymers of styrene/maleic acid and mixtures thereof typically willhave a molecular weight of at least about 50,000 and more preferablyfrom about 75,000 to about 300,000.

Preferred biocompatible polymers include cellulose diacetate andethylene vinyl alcohol copolymer. In one embodiment, the cellulosediacetate has an acetyl content of from about 31 to about 40 weightpercent. Cellulose diacetate polymers are either commercially availableor can be prepared by art recognized procedures. In a preferredembodiment, the number average molecular weight, as determined by gelpermeation chromatography, of the cellulose diacetate composition isfrom about 25,000 to about 100,000 more preferably from about 50,000 toabout 75,000 and still more preferably from about 58,000 to 64,000. Theweight average molecular weight of the cellulose diacetate composition,as determined by gel permeation chromatography, is preferably from about50,000 to 200,000 and more preferably from about 100,000 to about180,000. As is apparent to one skilled in the art, with all otherfactors being equal, cellulose diacetate polymers having a lowermolecular weight will impart a lower viscosity to the composition ascompared to higher molecular weight polymers. Accordingly, adjustment ofthe viscosity of the composition can be readily achieved by mereadjustment of the molecular weight of the polymer composition.

Ethylene vinyl alcohol copolymers comprise residues of both ethylene andvinyl alcohol monomers. Small amounts (e.g., less than 5 mole percent)of additional monomers can be included in the polymer structure orgrafted thereon provided such additional monomers do not alter theimplanting properties of the composition. Such additional monomersinclude, by way of example only, maleic anhydride, styrene, propylene,acrylic acid, vinyl acetate and the like.

Ethylene vinyl alcohol copolymers are either commercially available orcan be prepared by art recognized procedures. Preferably, the ethylenevinyl alcohol copolymer composition is selected such that a solution of8 weight-volume percent of the ethylene vinyl alcohol copolymer in DMSOhas a viscosity equal to or less than 60 centipoise at 20° C. and morepreferably 40 centipoise or less at 20° C. As is apparent to one skilledin the art, with all other factors being equal, copolymers having alower molecular weight will impart a lower viscosity to the compositionas compared to higher molecular weight copolymers. Accordingly,adjustment of the viscosity of the composition as necessary for catheterdelivery can be readily achieved by mere adjustment of the molecularweight of the copolymer composition.

As is also apparent, the ratio of ethylene to vinyl alcohol in thecopolymer affects the overall hydrophobicity/hydrophilicity of thecomposition which, in turn, affects the relative watersolubility/insolubility of the composition as well as the rate ofprecipitation of the copolymer in an aqueous solution. In a particularlypreferred embodiment, the copolymers employed herein comprise a molepercent of ethylene of from about 25 to about 60 and a mole percent ofvinyl alcohol of from about 40 to about 75, more preferably a molepercent of ethylene of from about 40 to about 60 and a mole percent ofvinyl alcohol of from about 40 to about 60.

The term “contrast agent” refers to a biocompatible (non-toxic)radiopaque material capable of being monitored during injection into amammalian subject by, for example, radiography. The contrast agent canbe either water soluble or water insoluble. Examples of water solublecontrast agents include metrizamide, iopamidol, iothalamate sodium,iodomide sodium, and meglumine. The term “water insoluble contrastagent” refers to contrast agents which are insoluble in water (i.e., hasa water solubility of less than 0.01 milligrams per milliliter at 20° C.) and include tantalum, tantalum oxide and barium sulfate, each of whichis commercially available in the proper form for in vivo use andpreferably having a particle size of 10 μm or less. Other waterinsoluble contrast agents include gold, tungsten and platinum powders.Methods for preparing such water insoluble biocompatible contrast agentshaving an average particle size of about 10 μm or less are describedbelow. Preferably, the contrast agent is water insoluble (i.e., has awater solubility of less than 0.01 mg/ml at 20° C. )

The term “biocompatible solvent” refers to an organic material liquid atleast at body temperature of the mammal in which the biocompatiblepolymer is soluble and, in the amounts used, is substantially non-toxic.Suitable biocompatible solvents include, by way of example,dimethylsulfoxide, analogues/homologues of dimethylsulfoxide, ethanol,ethyl lactate, acetone, and the like. Aqueous mixtures with thebiocompatible solvent can also be employed provided that the amount ofwater employed is sufficiently small that the dissolved polymerprecipitates upon injection into a human body. Preferably, thebiocompatible solvent is ethyl lactate or dimethylsulfoxide.

The term “encapsulation” as used relative to the contrast agent beingencapsulated in the precipitate is not meant to infer any physicalentrapment of the contrast agent within the precipitate much as acapsule encapsulates a medicament. Rather, this term is used to meanthat an integral coherent precipitate forms which does not separate intoindividual components, for example into a copolymer component and acontrast agent component.

The compositions employed in the methods of this invention are preparedby conventional methods whereby each of the components is added and theresulting composition mixed together until the overall composition issubstantially homogeneous. For example, sufficient amounts of theselected polymer are added to the biocompatible solvent to achieve theeffective concentration for the complete composition. Preferably, thecomposition will comprise from about 2.5 to about 8.0 weight percent ofthe polymer based on the total weight of the composition and morepreferably from about 4 to about 5.2 weight percent. If necessary,gentle heating and stirring can be used to effect dissolution of thepolymer into the biocompatible solvent, e.g., 12 hours at 50° C.

Sufficient amounts of the contrast agent are then optionally added tothe biocompatible solvent to achieve the effective concentration for thecomplete composition. Preferably, the composition will comprise fromabout 10 to about 40 weight percent of the contrast agent and morepreferably from about 20 to about 40 weight percent and even morepreferably about 30 to about 35 weight percent. When the contrast agentis not soluble in the biocompatible solvent, stirring is employed toeffect homogeneity of the resulting suspension. In order to enhanceformation of the suspension, the particle size of the contrast agent ispreferably maintained at about 10 μm or less and more preferably at fromabout 1 to about 5 μm (e.g., an average size of about 2 μm). In onepreferred embodiment, the appropriate particle size of the contrastagent is prepared, for example, by fractionation. In such an embodiment,a water insoluble contrast agent such as tantalum having an averageparticle size of less than about 20 microns is added to an organicliquid such as ethanol (absolute) preferably in a clean environment.Agitation of the resulting suspension followed by settling forapproximately 40 seconds permits the larger particles to settle faster.Removal of the upper portion of the organic liquid followed byseparation of the liquid from the particles results in a reduction ofthe particle size which is confirmed under an optical microscope. Theprocess is optionally repeated until a desired average particle size isreached.

The particular order of addition of components to the biocompatiblesolvent is not critical and stirring of the resulting suspension isconducted as necessary to achieve homogeneity of the composition.Preferably, mixing/stirring of the composition is conducted under ananhydrous atmosphere at ambient pressure. The resulting composition isheat sterilized and then stored preferably in sealed amber bottles orvials until needed.

Each of the polymers recited herein is commercially available but canalso be prepared by methods well known in the art. For example, polymersare typically prepared by conventional techniques such as radical,thermal, UV, gamma irradiation, or electron beam induced polymerizationemploying, as necessary, a polymerization catalyst or polymerizationinitiator to provide for the polymer composition. The specific manner ofpolymerization is not critical and the polymerization techniquesemployed do not form a part of this invention. In order to maintainsolubility in the biocompatible solvent, the polymers described hereinare preferably not cross-linked.

In another particularly preferred embodiment of the nonaqueous solution,the biocompatible polymer composition can be replaced with abiocompatible prepolymer composition containing a biocompatibleprepolymer. In this embodiment, the composition comprises abiocompatible prepolymer, an optional biocompatible water insolublecontrast agent preferably having an average particle size of about 10 μmor less and, optionally, a biocompatible solvent.

The term “biocompatible prepolymer” refers to materials which polymerizein situ to form a polymer and which, in the amounts employed, arenon-toxic, chemically inert, and substantially non-immunogenic when usedinternally in the patient and which are substantially insoluble inphysiologic liquids. Such a composition is introduced into the body as amixture of reactive chemicals and thereafter forms a biocompatiblepolymer within the body. Suitable biocompatible prepolymers include, byway of example, cyanoacrylates, hydroxyethyl methacrylate, siliconprepolymers, and the like. The prepolymer can either be a monomer or areactive oligomer. Preferably, the biocompatible prepolymer is alsonon-inflammatory when employed in situ.

Prepolymer compositions can be prepared by adding sufficient amounts ofthe optional contrast agent to the solution (e.g., liquid prepolymer) toachieve the effective concentration for the complete polymercomposition. Preferably, the prepolymer composition will comprise fromabout 10 to about 40 weight percent of the contrast agent and morepreferably from about 20 to about 40 weight percent and even morepreferably about 30 weight percent. When the contrast agent is notsoluble in the biocompatible prepolymer composition, stirring isemployed to effect homogeneity of the resulting suspension. In order toenhance formation of the suspension, the particle size of the contrastagent is preferably maintained at about 10 μm or less and morepreferably at from about 1 to about 5 μm (e.g., an average size of about2 μm).

When the prepolymer is liquid (as in the case of polyurethanes), the useof a biocompatible solvent is not absolutely necessary but may bepreferred to provide for an appropriate viscosity in the nonaqueoussolution. Preferably, when employed, the biocompatible solvent willcomprise from about 10 to about 50 weight percent of the biocompatibleprepolymer composition based on the total weight of the prepolymercomposition. When a biocompatible solvent is employed, the prepolymericcomposition typically comprises from about 90 to about 50 weight percentof the prepolymer based on the total weight of the composition.

In a particularly preferred embodiment, the prepolymer is cyanoacrylatewhich is preferably employed in the absence of a biocompatible solvent.When so employed, the cyanoacrylate adhesive is selected to have aviscosity of from about 5 to about 20 centipoise at 20° C.

The particular order of addition of components is not critical andstirring of the resulting suspension is conducted as necessary toachieve homogeneity of the composition. Preferably, mixing/stirring ofthe composition is conducted under an anhydrous atmosphere at ambientpressure. The resulting composition is sterilized and then storedpreferably in sealed amber bottles or vials until needed.

Specific embodiments of nonaqueous solutions suitable for use in theapparatus and methods of the invention are described in U.S. Pat. No.5,667,767 dated Sep. 16, 1997, U.S. Pat. No. 5,580,568 dated Dec. 3,1996 and U.S. Pat. No. 5,695,480 dated Dec. 9, 1997 and InternationalPublication Number WO 97/45131 having an International Publication Dateof Dec. 4, 1997, the entire contents of which are incorporated herein bythis reference.

In operation and use of treatment device 21 in the method of the presentinvention, syringe 91 is filled with the nonaqueous solution inpreparation of the procedure. The syringe 91 is loaded into gun 111 byopening cover portion 114 to permit placement of barrel 92 withinhousing 112. Ring 138 is grasped to pull rod 136 rearwardly relative tohousing 112 so that paddle 137 is disposed behind the retracted plunger94. Cover portion 114 is closed and secured to base portion 113 by meansof latch 117. The physician thereafter pulls trigger 141 as necessary tocause paddle 137 to engage the rear of plunger 94.

Although the method of the present invention permits supply assembly 27to be attached to needle assembly 26 after needle 61 and sleeve 62 havebeen disposed in working channel 51 of probe 22, the methodalternatively permits the supply assembly 26 to be attached to theneedle assembly prior to such disposition of the needle assembly withinprobe 22. In either case, attachment is accomplished by coupling firstluer fitting portion 104 of manifold 98 to luer fitting portion 93 ofsyringe 91 and second luer fitting portion 106 of the manifold to thefirst luer fitting portion 83 of fluid connector 81. Coupler 173 ispivoted downwardly so that first and second arms 176 thereof engage grip82 and screw 179 is tightened to secure the grip 82 in the slot 178between arms 176. Thumb screw 172 is rotated in a counterclockwisedirection relative to rear post 191 to ensure that needle 61 is fullyretracted within sleeve 62. Thereafter, saline solution syringe 97 iscoupled by means of tube 110 to third luer fitting portion 107 of themanifold 98 and DMSO syringe 96 is coupled by means of tube 109 tofourth luer fitting portion 108 of the manifold.

Probe 22 is prepared by connecting light cable 46 to light source 47 andattaching the proper eyepiece 41 to handle 33. In addition, all otherconventional attachments are applied to the probe 22.

After the patient has been appropriately sedated or anesthetized, probedistal extremity 31 b is introduced through mouth 187 into esophagus191. In this regard, probe handle 33 is grasped by the physician tointroduce distal extremity 31 b of probe 22 into mouth 187 and advancethe insertion tube 31 down esophagus 191 to the vicinity of the varix207. Optical viewing device 23 facilities such advancement by thephysician of insertion tube 31. Insertion tube 31 has a length so thatwhen distal extremity 31 b is in the vicinity of the varix 207, proximalextremity 31 a is outside of body 184.

Distal end portions 61 b and 62 b of needle assembly 26 are now insertedthrough side port 52 of insertion tube 31 and advanced until such distalend portions of needle 61 and sleeve 62 are in the vicinity of insertiontube distal extremity 31 b. Needle 61 and sleeve 62 are each movablefrom a first position in which distal end portions 61 b and 62 b areeach retracted within insertion tube 31 and thus recessed within workingchannel 51 to a second position in which the distal end portions 61 band 62 b extend distally beyond the end of insertion tube 31. The needleand sleeve each have a sufficient length so that the physician holdinggun 111 can extend both the needle and the sleeve distally from distalextremity 31 b a significant distance, should that be desired.

A portion of the procedure for treating varices 207 is shown in FIGS. 6and 7. Under the guidance of optical viewing device 23, insertion tubedistal extremity 31 b is maneuvered to a position above the varix 207 tobe treated. The physician retracts sleeve 62 relative to needle 61 bymeans of adjustment mechanism 166 so that needle distal end portion 61 bextends beyond sleeve distal end portion 62 b a selected amount of atleast 2 millimeters and preferably ranging from 2 to 15 millimeters.Such amount of extension can be easily determined for example bycorrelating such extension as a function of the rotation of thumb screw172 and properly calibrating the position of thumb screw 172 relative torear post 168 in this regard. The retraction of needle 61 relative tosleeve 62 can occur either within working channel 51 or after the needle61 and sleeve 62 have been extended from insertion tube distal extremity31 b.

The physician optionally cleanses needle passage 63 with DMSO fromsyringe 96. DMSO cleansing can be determined by observing a slightamount of DMSO being dispelled from needle distal end portion 61 b. TheDMSO is then removed from passage 63 by withdrawing the plunger ofsyringe 96 or by any other suitable means. The cleansing of the passagewith DMSO inhibits premature precipitation within syringe 91 of thebiocompatible polymer in the nonaqueous solution from the DMSO in thenonaqueous solution. Needle passage 63 is next primed with thenonaqueous solution carried by syringe 91 until such solution isavailable at the openings 71 in needle distal end portion 61 b. Forsimplicity, the operation of conventional stop cocks 101-103 fordirecting appropriate fluids to and from needle passage 63 will not bediscussed in connection with the procedure.

The nonaqueous solution is injected into blood vessel 207 in thevicinity of the varix 208 to be treated and preferably proximal orupstream of the varix 208. The physician positions insertion tube distalextremity 31 b in the esophagus and causes sharpened end 67 of needle 61to penetrate wall 188 and thus extend into the blood vessel 207 bymoving the needle 61 and sleeve 62 closer to side port 52. The field ofview of optical viewing device 23 permits the physician to observe thepenetration of blood vessel 207. Although the needle 61 and sleeve 62can penetrate the wall 188 at any angle, it is preferred that the angleof penetration relative to wall 188 be less than 90° and more preferablyless than 40°. The physician pulls trigger 141 to cause the desiredpreselected amount of nonaqueous solution to be introduced throughneedle 61 extending through probe 22. The openings 71 in needle distalend portion 61 b are positioned in wall 193 so that the nonaqueoussolution is introduced into the blood vessel. The optional contrastagent within the nonaqueous solution permits the viewing of thenonaqueous solution by means of fluoroscopy. In addition, theintroduction of the nonaqueous solution into wall 188 can be monitoredtransabdominally or transesophageally by ultrasound. The rate ofinjection of the nonaqueous solution into blood vessel 207 can rangefrom 0.1 cc per minute to 10 cc per minute. The amount of nonaqueoussolution so injected into the blood vessel 207 can range from 0.05 to 10cc and preferably range from 0.25 to 3 cc.

Once the nonaqueous solution has been introduced into the blood vessel207, the biocompatible polymer of the nonaqueous solution precipitatesto form one or more discrete deposits or solid implants 213 in the bloodvessel (see FIGS. 7 and 8). The amount of nonaqueous solution injectedinto wall 188 for each implant can range from 0.05 cc to 10 cc. Althoughonly a single implant 213 is shown as being created in blood vessel 207,a plurality of implants 213 can be created in the blood vessel. The oneor more implants 213 are formed in the vicinity of each varix 208 andpreferably in the proximal portion 208 a of the varix 208 or in thevessel 207 proximal of the varix 208. However, an implant 213 can alsobe formed in varix distal portion 208 b. Each implant 213 substantiallyconforms to the shape of the blood vessel 208. Implants 213 which mergewith adjacent implants in blood vessel 207 are within the scope of thepresent invention. It is preferable that each implant 213 be sized andshaped to completely occlude the blood vessel 207 and thus precludeblood flow past the implant 213 (see FIG. 8).

A saline or other aqueous or physiologic solution can optionally beintroduced into the blood vessel 207 after the introduction of thenonaqueous solution in the blood vessel 207 to facilitate dispersion ofthe DMSO or other biocompatible solvent present in the nonaqueoussolution.

The occlusion of the blood vessel caused by the implant 213 terminatesblood flow beyond the implant and thus ceases any bleeding of the varix208 beyond the implant. The cessation of blood flow beyond the implanteventually causes the varix 208 to atrophy and disappear. The procedureof the invention can optionally be performed in combination withligatures, sclerosing agents, tissue glues and clotting agents.

The method of the present invention is broad enough to cover thetreatment of vessels in any internal wall of the body. In a furtherexample, the method of the invention can be utilized to treat ulcers inthe gastrointestinal tract and more specifically to treat ulcers in thecardia (see FIGS. 9 and 10). Ulcer 221 has a crater 222 formed in thegastric mucosa and has a blood vessel 207 such as blood vessel 223having an exposed portion 223 a. The vessel 223 has an opening 224 inthe exposed portion through which the blood 226 of the vessel isflowing. Any suitable device such as treatment device 21 can be utilizedin such procedure.

The method of the present invention for treating ulcers is substantiallysimilar to the method described above for treating varices. In general,and as more specifically described above, probe distal extremity 31 b isintroduced through mouth 198 into esophagus 191 and distal end portions61 b and 62 b of needle assembly 26 advanced through insertion tube 31until such distal end portions are in the vicinity of insertion tubedistal extremity 31 b. Under the guidance of optical viewing device 23,insertion tube distal extremity 31 b is maneuvered to a position abovethe ulcer 221 to be treated. After optionally cleansing needle passage63 with DMSO, the needle passage is primed with any suitable solutionsuch as the nonaqueous solution discussed above.

The nonaqueous solution is injected by the physician into vessel 223 inthe vicinity of the exposed portion 223 a and preferably proximal orupstream of the opening 224. The physician positions insertion tubedistal extremity 31 b in the cardia and causes sharpened end 67 ofneedle 61 to penetrate vessel 223 by moving the needle 61 and sleeve 62closer to side port 52. The field of view of optical viewing device 23permits the physician to observe the penetration of vessel 223. Thephysician pulls trigger 141 to cause the desired preselected amount ofnonaqueous solution to be introduced through needle 61 and the one ormore of openings 71 disposed in the vessel 223. The optional contrastagent within the nonaqueous solution permits the viewing of thenonaqueous solution by means of fluoroscopy. In addition, theintroduction of the nonaqueous solution into the vessel 223 can bemonitored transabdominally or transesophageally by ultrasound. The rateof injection of the nonaqueous solution into vessel 223 can range from0.1 cc per minute to 10 cc per minute. The amount of nonaqueous solutionso injected into the vessel 223 can range from 0.05 to 10 cc andpreferably range from 0.25 to 3 cc.

Once the nonaqueous solution has been introduced into the vessel 223,the biocompatible polymer of the nonaqueous solution precipitates toform one or more discrete deposits or solid implants 227 in the vessel(see FIGS. 9 and 10). The amount of nonaqueous solution injected intoulcer 221 for each implant can range from 0.05 cc to 10 cc. First andsecond implants 227 a and 227 b are shown in vessel 223 in FIG. 10. Itis preferable that at least one of the implants 227 a be formed upstreamof the opening 224. The second implant 227 b in FIG. 10 is formeddownstream of the opening 224 to inhibit any retrograde blood flow fromthe opening. Although only two implants 227 are shown as being createdin vessel 223, one or a plurality of implants 227 can be created in thevessel. Each implant 227 is sized and shaped in a manner similar toimplants 213 discussed above with respect to varices 208. Morespecifically, it is preferable that each implant 227 be sized and shapedto completely occlude the vessel 223 and thus preclude blood flow pastthe implant 227 (see FIG. 10). A saline or other aqueous or physiologicsolution can optionally be introduced into the vessel 223 forfacilitating the dispersion of the DMSO or other biocompatible solventpresent in the nonaqueous solution.

The occlusion of vessel 223 caused by the implant 227 terminates bloodflow beyond the implant and thus ceases any bleeding of the ulcer 221beyond the implant. The cessation of blood flow beyond the implant 227eventually causes the portion of vessel 223 distal of the implant toatrophy. The procedure of the invention can be used with used withcauterizing and/or clotting agents.

Additional implants 228 can be formed in the wall 193 forming stomach188 for creating a tamponade to inhibit blood flow from opening 224.Several of such implants 228 are shown in muscle layers 201 and 202 inFIG. 10. The implants 228 are substantially similar to the implantsdescribed above and can be formed in the manner described above. Itshould be appreciated that implants 228 for the tamponade can be formedin all or any of the layers forming wall 193.

Other supply and/or injection assemblies, such as any of those describedin copending U.S. patent application Ser. No. 09/232,056 filed Jan. 15,1999, can be used with probe 22 and needle assembly 26 in the methods ofthe invention for treating vessels 207 in the upper gastrointestinaltract. In addition, such methods are not limited to the transesophagealor intraesophageal methods described above. The methods herein can alsobe performed by surgical procedures such as a laparotomy, thoracotomy,laparoscopy or thoracoscopy.

In a further specific method of the present invention, the method can beused to treat one or more vessels such as hemorrhoids 231 located in thelower portion of the gastrointestinal tract (see FIGS. 11 and 12). Suchlower portion of the gastrointestinal tract includes the anal canal orrectum 232 and opens to the outside of body 184 at the anus 233. Theinner layer of the rectal wall 236 forming rectum 232 is mucosal layer237. A layer of muscle extends around the rectum 232 and also forms partof rectal wall 236. Such muscle layer comprises circular muscle layer241 extending beneath mucosal layer 237 and longitudinal muscle layer242 extending beneath muscle layer 241. Body 184 further includes theanal sphincter 246 having the sphincter ani internus 247 and thesphincter ani externus 248. The sphincter ani internus 247 forms theterminus of circular muscle layer 241 at anus 233. The sphincter aniexternus 248 comprises a deep external sphincter 251, the superficialexternal sphincter 252 and the subcutaneous external sphincter 253. Forpurposes of this application, rectal wall 236 and thus the wall of thegastrointestinal tract of body 184 includes both the sphincter aniinternus 247 and the sphincter ani externus 248. Hemorrhoids 231 areformed from a plurality of blood vessels 256 having enlarged portions256 a and can be internal or external of rectal wall 236.

In the method of the present invention for treating hemorrhoids 231, asolution is introduced into the vessels or blood vessels 256 forming thehemorrhoids to occlude blood flow to the enlarged portion 256 a of thehemorrhoid. One preferred apparatus for introducing the solution intohemorrhoids 231 is a conventional syringe 261 having a barrel 262 filledwith any suitable solution such as the nonaqueous solution discussedabove. A conventional elongate needle 263 is connected to syringe 261for delivering the solution from barrel 262 into the hemorrhoid. Tubularneedle 263 can be of a conventional type and, as such, provided with asingle opening at the distal end thereof. Alternatively, needle 263 canbe similar to any of the needles described above.

The nonaqueous solution is injected by the physician into blood vessel256 in the vicinity of the enlarged portion 256 a and preferablyproximal of the enlarged portion 256 a. In this regard, the physicianintroduces the needle 263 through anus 233 and into rectum 232 andthereafter causes the sharpened end of needle 263 to penetrate bloodvessel 256. The physician pushes down on the syringe plunger to causethe desired preselected amount of nonaqueous solution to be introducedthrough the needle into the blood vessel. The optional contrast agentwithin the nonaqueous solution permits the viewing of the nonaqueoussolution by means of fluoroscopy. The rate of injection of thenonaqueous solution into blood vessel 256 can range from 0.1 cc perminute to 10 cc per minute. The amount of nonaqueous solution soinjected into the blood vessel 256 can range from 0.05 to 10 cc andpreferably range from 0.25 to 3 cc.

Once the nonaqueous solution has been introduced into the blood vessel256, the biocompatible polymer of the nonaqueous solution precipitatesto form one or more discrete deposits or solid implants 266 in thehemorrhoid 231 (see FIGS. 11 and 12). The amount of nonaqueous solutioninjected into the hemorrhoid 231 for each implant can range from 0.05 ccto 10 cc. Although only a single implant 266 is shown as being createdin the hemorrhoid 231, a plurality of implants 266 can be created in thehemorrhoid. The one or more implants 266 are formed in the vicinity ofenlarged portion 256 a and preferably proximal of the enlarged portion256 a of the hemorrhoid 231. Each implant 266 is sized and shaped in amanner similar to implants 213 discussed above with respect to varices208. More specifically, it is preferable that each implant 266 be sizedand shaped to completely occlude the blood vessel 256 and thus precludeblood flow past the implant 266 (see FIG. 12). A saline or other aqueousor physiologic solution can optionally be introduced into the bloodvessel 256 for facilitating the dispersion of the DMSO or otherbiocompatible solvent present in the nonaqueous solution.

The occlusion of blood vessel 256 caused by the implant 266 terminatesblood flow beyond the implant and thus ceases any bleeding of thehemorrhoid 231 beyond the implant. Such cessation of blood floweventually causes the hemorrhoid 231 to atrophy and disappear. Theprocedure hereof for treating hemorrhoids can be used in combinationwith ligatures.

Other apparatus can be utilized for treating hemorrhoids 231 inaccordance with the method of the present invention. For example,apparatus of the type disclosed in U.S. patent application Ser. No.09/286,245, the entire contents of which are incorporated herein by thisreference, can also be utilized in the method hereof.

The needle assembly of the present invention can have otherconfigurations. For example, the needles disclosed herein can beprovided with a plurality of lumens or passages extending longitudinallytherethrough for permitting multiple liquids to be separately carried bythe needle. In a further alternative embodiment, a plurality of needlescan be introduced through the working channels of any suitable probesuch as probe 22 or otherwise utilized in the methods disclosed herein.Each of such needles can be used to perform one or more of the steps ofthe invention. For example, separate needles can be provided for theintroduction of the nonaqueous solution, for the introduction of theDMSO or other biocompatible solvent and for the introduction of thesaline solution or other physiologic or aqueous solution.

In addition, although the method and apparatus of the invention havebeen described as utilizing a biocompatible polymer and a biocompatiblesolvent, the method and apparatus can be modified as necessary whenother solutions such as those containing prepolymers are utilized. Itshould be appreciated that the syringes or other reservoirs describedherein can be manually operated, as shown, or automated. For example, aconventional single-speed, multi-speed, programmable or other syringepump can be used for automation. Further, in procedures where no salineor similar solution is utilized, the saline solution syringe and therelated saline solution fluid flow hardware need not be provided in thetreatment device.

It should be appreciated that the implants of the present invention canbe used as delivery vehicles for other materials such as radioisotopes,chemotherapeutic agents, anti-inflammatory agents and/or antibiotics.The optional contrast agent in the implants permits the implants to bemonitored after completion of the procedure described above. Thus thestability of the implant and its configuration can be observed overtime. Further procedures can be performed to supplement previouslyformed implants.

From the foregoing, it can be seen that a minimally invasive method forinjecting a material into a vessel of the gastrointestinal tract of abody to substantially occlude the vessel has been provided. The injectedmaterial can be a nonbiodegradable material and, preferably, can be atleast one solution which forms a solid in the vessel. The at least onesolution can include a solution from which a nonbiodegradable solidprecipitates. The solution is preferably a biocompatible polymer and abiocompatible solvent.

What is claimed is:
 1. A method for use in a body of a mammal having aninternal wall forming a gastrointestinal tract to treat a blood vesselin the wall having a portion comprising the steps of introducing atleast one nonaqueous solution from the gastrointestinal tract into thevessel and forming from the at least one nonaqueous solution anonbiodegradable solid in the vessel in the vicinity of the portion tocreate an occlusion in the vessel and thus terminate blood flow to thevessel distal of the occlusion.
 2. The method of claim 1 wherein the atleast one solution is a solution of a biocompatible polymer and abiocompatible solvent and wherein the forming step includes the step ofprecipitating the biocompatible polymer from the solution so that thebiocompatible polymer solidifies in the vessel and the biocompatiblesolvent disperses in the body.
 3. The method of claim 2 wherein thesolution of the biocompatible polymer and the biocompatible solvent hasa composition comprising from about 2.5 to about 8.0 weight percent of abiocompatible polymer, from about 10 to about 40 weight percent of awater insoluble biocompatible contrast agent and from about 52 to about87.5 weight percent of a biocompatible solvent.
 4. The method of claim 2wherein the solution of the biocompatible polymer and the biocompatiblesolvent has a composition comprising from about 2.5 to about 8.0 weightpercent of a biocompatible polymer, from about 10 to about 40 weightpercent of a water soluble biocompatible contrast agent and from about52 to about 87.5 weight percent of a biocompatible solvent.
 5. Themethod of claim 1 wherein the introducing step includes the steps ofextending a needle into the vessel and supplying the at least onesolution through the needle into the vessel.
 6. The method of claim 5wherein the introducing step includes the step of introducing the needlethrough the mouth and into the gastrointestinal tract.
 7. The method ofclaim 6 wherein the portion of the vessel is an enlarged varix in thevicinity of the gastroesophageal sphincter.
 8. The method of claim 6wherein the portion of the vessel is an ulcer in the gastrointestinaltract.
 9. The method of claim 5 wherein the introducing step includesthe step of introducing the needle through the anus and into the analcanal of the gastrointestinal tract.
 10. The method of claim 9 whereinthe portion of the vessel is a hemorrhoid in the anal canal.
 11. Themethod of claim 1 wherein the portion of the vessel is an enlarged varixin the vicinity of the gastroesophageal sphincter.
 12. The method ofclaim 1 wherein the portion of the vessel is an ulcer.
 13. The method ofclaim 12 further comprising the step of forming at least one implant inthe wall in the vicinity of the gastrointestinal tract to create atamponade.
 14. The method of claim 1 wherein the portion of the vesselis a hemorrhoid in the anal canal.
 15. The method of claim 1 wherein themammal is a human.
 16. The method of claim 1 further comprising the stepof ligating the portion of the vessel.
 17. The method of claim 1 furthercomprising the step of introducing a clotting agent into the vessel inthe vicinity of the portion.
 18. The method of claim 1 furthercomprising the step of cauterizing the vessel in the vicinity of theportion.
 19. A method for treating a varix in a gastrointestinal wall ofa body of a mammal having a blood vessel in the wall leading to thevarix comprising the steps of extending a needle through the wall intothe blood vessel and introducing an implant forming material into thevessel to form an implant in the vessel so as to occlude the vessel andthus limit blood flow to the varix.
 20. The method of claim 19 whereinthe implant is a nonbiodegradable implant.
 21. The method of claim 19further comprising the step of ligating the varix.
 22. A method fortreating an ulcer in a gastrointestinal wall of a body of a mammalhaving a blood vessel in the wall leading to the ulcer comprising thesteps of extending a needle through the wall into the blood vessel andintroducing an implant forming material into the vessel to form animplant in the vessel so as to occlude the vessel and thus limit bloodflow to the ulcer.
 23. The method of claim 22 wherein the implant is anonbiodegradable implant.
 24. The method of claim 22 further comprisingthe step of creating a tamponade in the wall in the vicinity of theulcer to inhibit bleeding of the ulcer.
 25. The method of claim 24wherein the creating step includes the step of forming a plurality ofimplants in the wall in the vicinity of the ulcer.
 26. The method ofclaim 25 wherein the wall includes a muscle layer, the creating stepincluding the step of forming a plurality of implants in the musclelayer of the wall.
 27. A method for treating a hemorrhoid in a rectalwall of a body of a mammal having a blood vessel in the wall leading tothe hemorrhoid comprising the steps of extending a needle through thewall into the blood vessel and introducing an implant forming materialinto the vessel to form an implant in the vessel so as to occlude thevessel and thus limit blood flow to the hemorrhoid.
 28. The method ofclaim 27 wherein the implant is a nonbiodegradable implant.
 29. Themethod of claim 27 further comprising the step of ligating thehemorrhoid.
 30. A method for use in a body of a mammal having aninternal wall forming a gastrointestinal tract to treat a blood vesselin the wall having a portion comprising the steps of injecting animplant forming material into the vessel in the wall and forming fromsuch material at least one implant in the vessel in the vicinity of theportion to create an occlusion in the vessel and thus limit blood flowto the vessel distal of the occlusion.
 31. The method of claim 30further comprising the step of ligating the portion of the vessel. 32.The method of claim 30 further comprising the step of creating atamponade in the wall in the vicinity of the portion.
 33. A method fortreating an ulcer in a gastrointestinal wall of a body of a mammalcomprising the step of forming a plurality of implants in the wall inthe vicinity of the ulcer to create a tamponade and thus inhibit bloodflow to the ulcer.
 34. The method of claim 33 wherein the wall includesa muscle layer, the forming step including the step of forming aplurality of implants in the muscle layer of the wall.
 35. A method fortreating a vessel in a gastrointestinal wall of a body of a mammalcomprising the step of forming at least one implant in the wall in thevicinity of the vessel to create a tamponade and thus inhibit blood flowin the vessel distal of the tamponade.
 36. The method of claim 35wherein the forming step includes the step of forming a plurality ofimplants in the wall in the vicinity of the vessel to create thetamponade.
 37. The method of claim 35 wherein the at least one implantis a nonbiodegradable implant.